both Rx and OTC.
I’ve always assumed when a medication expires, it just becomes less effective as the active ingredient decays. So expired medication isn’t harmful, just less effective.
But I’ve heard some antibiotics can become toxic if used after they expire.
Is there a factual answer?
Harvard Medical School: “Drug Expiration Dates — Do They Mean Anything?“
Propublica.org: “The Myth of Drug Expiration Dates”
ConsumerMedSafety.org “What does a medicine’s expiration date mean?”
Except for nitroglycerin, insulin, and liquid antibiotics, most drugs will retain their potency well past the expiration date. Some drugs like albuterol or epinephrine which are stored in volatile substrates as an inhalant or injector will gradually loose effectiveness, especially if not stored in controlled condictions, but are not unsafe to use.
Stranger
From my experience:
Codeine cough syrup is fine decades after it was bottled, but I had to take less because some of the alcohol had evaporated, so it was more potent.
I used the same bottle of Afrin for probably a decade after it expired. It got weaker, and I eventually replaced it, but a slightly larger dose worked fine until I bought the new one.
Aspirin works until the vinegar smell is overwhelming.
Ranitidine that was only slightly past its expiration date tasted nasty and didn’t work.
So it varies a lot by drug. I haven’t yet been poisoned (that I noticed) by using expired drugs. But I’ve certainly run into ones that stopped working.
I’ve taken Isosorbide dinitrate (“Isordil”, a nitroglycerin substitute) both in 20mg dose and in the 5mg sublingual dose. I don’t know about potency for its therapeutic effect, but when I take years-old Isordil I get a horrible head-ache that may last for more than one day.
(But Headache is a normal side-effect and I’ve not done the controlled experiments to be absolutely certain medicine age is correlated with headache severity.)
Cecil calls the claims that tetracycline turns into poison “dubious,” but Mayo and Merck both still warn against using it after it expires.
Just as background, the shelf life is a reflection of how long a medicine complies with its specification, but the ways a medicine can be non-compliant are many and varied, and the nature and “seriousness” of the non-compliance will vary on a case-by-case basis.
For example:
A solid medicine may be hygroscopic (typically we’re talking about multidose containers rather than, say, tablets in blisters). Taking up water per se may not be disastrous, but it can affect the physical and chemical stability of the medicine. (Conversely, infusion liquids can lose water (diffusion through the bag) and increase in concentration.)
Active substances may decompose. So you get a loss of active but, potentially more significant, it degrades into something else, which may also have pharmacological activity, but not the type of activity you want. (When a drug molecule breaks up, you end up with another molecule rather similar in structure to its parent, but with a bit missing. So, very commonly decomposition products are also pharmacologically active. But the activity of the decomposition product may not be the same as the parent.)
Physical performance can be affected. A tablet may change in effectiveness because it doesn’t dissolve so well in the gut post-expiration.
Aspartame isn’t very stable in solution away from it’s optimum pH, so a sweetened syrup may start to taste foul beyond expiration.
Physical changes in a suspension product over time may make it harder and harder to resuspend for use.
Preservatives may decompose to the point where a product is no longer adequately preserved, which could lead to eg fungal growth. There are circumstances where this could be extremely serious.
Then there are things like pressurised aerosols (they all leak and lose pressure over time) or dry powder inhalers (which can take up water so that the powder gets sticky).
….and so on. This doesn’t take into account exotica like radiopharmaceuticals (for example), which may have an exceedingly short shelf life, and other weird and whacky medicines.
So, the shelf life is there for a reason, and there may be non-obvious consequences to using an expired product.
j
Note that keeping the drugs in a cool dry place will enhance that shelf life quite a bit.
If the get damp or hot for a expended period, yes they could go bad.
But in general that “use by date” is bogus, and I have no doubt that pills within say a year are good. five years? That could be problematic.
Here is a relevant report from JAMA Internal Medicine (referred to in Stranger’s link above).
The authors were able to assay long-forgotten prescription medicines that had been stored in their original, unopened containers.
From the article:
The article also includes an interesting table that lists (what are essentially) the percent of drug recovered for over 20 different agents.
Nothing like evidence.
Where to start? Just taking the paper on its own terms – are these drugs compliant on assay (“The US Food and Drug Administration (FDA) permits “reasonable variation,” such that most medications marketed in the United States contain 90% to 110% of the amount of the active ingredient claimed on the label”) – they tested 8 drug products:
Somnafac – fail on methaqualone assay
Florinal with Codeine No.1 – fail on aspirin assay (1% of label claim!!); fail on caffeine assay
Codempiral No.3 – fail on aspirin assay (< 1% of label claim!!); fail on phenacetin assay
Bamadex – fail on meprobamate assay; fail on amphetamine assay
Obocell - fail on amphetamine assay
Nebralin - fail on pentobarbital assay
Seconal – (marginal) pass
Hycomine - fail on chlorpheniramine assay
As the authors point out, some of these fails are for high assay results (>300% of label claim in the case of the Hycomine chlorpheniramine assay) (!! – go figure). In any case 7 of 8 drug products fail, mostly in a spectacular manner.
However, I assume this discussion is about fitness for purpose of expired drug products; and as I have already pointed out, the ways a medicine can be non-compliant with its specification are many and varied – and extend well beyond a simple potency assay.
Was the level of potentially toxic identified and unidentified impurities considered? No.
Was in vivo performance or an in vitro marker for performance (dissolution testing) considered? No.
Was microbial contamination considered? No.
I’m not going to waste my time going through other untested parameters that might be applicable to the individual drug products tested.
Evidence of fitness for purpose of expired drugs? This is, indeed, nothing like evidence.
In the setting of shelf lives, pharmaceutical companies have to meet the requirements of regulatory bodies (the FDA in the US) and are obliged to be somewhat conservative in interpretation of the totality of the data. Potency may not be a critical factor. Potency may remain high long after the dissolution rate of your tablets has changed significantly, for example. There are lots of ways to become unfit for purpose once the shelf life is exceeded.
Do I take expired medicines from time to time? Sure. But I do apply a bit of sense.
j
A major issue is that no one wants to pay to prove that old drugs are still good. A proper drug efficacy study would take years (just to age the drugs) and then the old medicines would have to be tested for safety and efficacy. It’s not in anyone’s interest to pay for that. The drug companies would prefer you buy new product. Who else really cares?
I have always believed that expired Tylenol could cause organ failure. Did I get it mixed up with tetracycline all these years, and was even wrong about that?
At least it never cost me anything. I don’t even take Tylenol, so I never have expired Tylenol.
I think this is important to be aware of. Many people keep medications in the bathroom, which is probably the worst place in the house to keep them. Daily doses of high humidity (showers) and heat can degrade the drugs more quickly. I keep all my medications in a closet away from the bathroom.
Not really true. The testing you are referring to is termed stability testing; it happens in development, but that isn’t the end of the matter. Whenever a significant change is made (like, for example, a change to the packaging type) more stability testing is required. And just to make sure that nothing unexpected is happening, there’s a legal obligation to stability test a minimum of one batch every year in which manufacturing takes place. So the data to provide an understanding of product stability, and to confirm the suitability of the shelf life, is always there. It is frequently this data that is used to extend shelf lives.
There seems to be a misapprehension that pharmaceutical companies want short shelf lives - absolutely not true, it’s the exact opposite. The longer the shelf life, the more stock flexibility you have. There are cost savings to be made - you can have bigger and less frequent manufacturing campaigns, which minimises set-up and cleandown costs, and equipment and facility downtime.
In practice, regulatory bodies will set an upper limit on shelf life simply because they don’t want packs with superseded package inserts on the shelves.
j
What does this mean? The ingredient was present at three times the amount that the manufacturer advertised!?!? Does this represent a problem with the underlying manufacturing process, or that other compounds are decaying into hycomine chlorpheniramine (seems unlikely) or what?
Yeah - you wonder, don’t you? There are basically two things you could question - the original manufacture and the analyses used in the published study. Re the latter, the fact that one of their analyses reports 300%+ of the label claim - well, you would have thought it merited specific comment.
As we don’t know anything about the manufacture and only have a brief publication (a letter,and so presumably not peer reviewed) to go on - dunno.
Here’s a thing, though - I just checked back to make sure they did not address that weird result, and I found this:
Looks like I wasn’t the only one to feel that the letter was - mmmmm - lacking. The abstract of the critique by Madden et al is here:
I don’t have access to the complete critique, but it sounds ike they had plenty to say.
j
I certainly wonder whether anyone is actually monitoring the annual batch testing you mentioned! Thanks for your very informative posts in this thread.
Since the question has been answered, I will add an anecdote
I have only had anxiety attacks of any degree twice - both after taking pseudo-ephedrine that was way past its expiration date. Thus, I now never take any medicine that is expired. I don’t want to know what other effects might occur
FWIW I just accidentally found the abstract of the paper in question: Reversible Fanconi Syndrome Caused by Degraded Tetracycline | JAMA | JAMA Network
j
My pleasure. Being fairly recently retired, I almost felt useful today.
j